Liver disease can develop in chronic hepatitis B (CHB) patients with normal or mildly elevated alanine aminotransferase (ALT) who seldom undergo liver biopsy. We aimed to determine histologic characteristics of a large cohort of Chinese CHB patients undergoing liver biopsy and to evaluate the utility of ALT and HBV DNA values at the time of biopsy in predicting liver disease in this population. This prospective study enrolled 230 treatment-naïve patients with persistently normal or mildly elevated ALT. All patients had a liver biopsy. ALT, aspartate aminotransferase (AST), and HBV DNA levels were some of the other parameters measured. Using Scheuer's classification, significant histology was defined as stage ≧2 fibrosis and/or stage 1 fibrosis plus≧ grade 2 inflammation. Liver disease was observed in 34.4% and 61.8% of patients with normal ALT and mildly elevated ALT, respectively. Patients with mildly elevated ALT levels had significantly more events, including liver disease, elevated AST, and moderate to severe inflammation and liver fibrosis, than patients with normal ALT (all P≤0.005). A total of 107 patients (46.5%) had liver disease and 123 (53.5%) did not. PLT and ALT were significantly associated with liver disease (both P<0.001). Patients with elevated ALT, lower platelet count and HBV DNA < 7 log10copies/mL may have histologically significant changes associated with liver disease. Multivariate analysis showed that PLT and HBV DNA levels were significantly associated with liver disease in patients with normal ALT while gender and HBV DNA levels were significantly associated with liver disease in patients with mildly elevated ALT. Assessing liver damage via biopsy in patients with normal or mildly elevated ALT may help to identify those who would benefit from antiviral therapy.
The proposed fibrosis scoring system predicted the probability of significant fibrosis in CHB patients with ALT levels 2-fold lower than the ULN with sufficient accuracy. It identified individuals with a very high risk for significant fibrosis in whom liver biopsy would most likely yield a diagnostic benefit. It also identified individuals with a low risk of moderate fibrosis in whom a liver biopsy can be delayed or avoided.
Abnormal lipid metabolism and SREBP‐1 downregulation are reported to be involved in the pathogenesis of diabetic peripheral neuropathy (DPN). In the current study, the relationship between PI3K/Akt signaling pathway and SREBP‐1 expression was explored in Schwann cells of DPN. The phospho‐Akt (Ser 473), phospho‐Akt (Thr 308), and SREBP‐1 expression were inhibited in the sciatic nerves of diabetic mice versus those of normal mice, accompanied with the atrophy of nerve fiber and the irregular myelin sheath. High concentration glucose suppressed phospho‐Akt (Ser 473), phospho‐Akt (Thr 308), and SREBP‐1 expression in cultured Schwann cell (RSC96 cell) in vitro, and 25 mmol/L glucose was enough to lead to the maximum inhibitory effect. The time‐course effect of high glucose showed that Akt phosphorylation gradually decreased with the extension of stimulation time. Somewhat differently, short‐term high‐glucose exposure enhanced SREBP‐1 expression and prolonged high‐glucose stimulation reduced the SREBP‐1 expression in RSC96 cells. Similarly, prolonged high‐glucose stimulation also downregulated FASN messenger RNA (mRNA), ACC mRNA, intracellular triglyceride, and cholesterol. LY294002 suppressed Akt activation followed by the decreased SREBP‐1, FASN, ACC, triglyceride, and cholesterol. Contrarily, the PI3K/Akt signaling pathway agonist insulin pretreatment avoided prolonged high‐glucose stimulation‐blocked Akt activation and increased SREBP‐1, FASN, and ACC expression in the levels of protein and mRNA in RSC96 cells. The knockdown of SREBP‐1 by shRNA prevented insulin‐induced enhanced FASN, ACC mRNA expression, triglyceride, and cholesterol in high‐glucose‐treated RSC96 cells. In conclusion, prolonged high‐glucose exposure inhibits the SREBP‐1/FASN/ACC expression in the Schwann cells of DPN via the blockage of the PI3K/Akt signaling pathway.
Geriatric population is increasing rapidly worldwide, and fragility fracture and complication following orthopaedic surgery in elderly people have now become major challenges for surgeons. Further studies are required to identify potentially modifiable factors associated with surgical site infection (SSI) in geriatric patients. This retrospective, multicenter study was conducted at four level I hospitals in China. During the 31-month study period, a total of 2341 patients (65 years or older) underwent orthopaedic surgery and complete data were recorded from September 2015 to April 2018. Demographics information, medications and additional comorbidities, surgery-related variables, and laboratory indexes were extracted and analysed. Receiver-operating characteristic analysis was performed to detect the optimum threshold of continuous variables. Independent risk factors of SSI were identified by univariate and multivariate analyses. Finally, 63 patients suffered from wound infection within the follow-up period, indicating a 2.7% incidence rate of SSI. Statistical results showed that open injury (odds ratio [OR], 9.5; 95% confidence interval [CI], 5.4-16.7), American Society of Anesthesiologists classified III-IV score (OR, 2.2; 95% CI, 1.3-3.8), surgical duration of >132 minutes (OR, 2.9; 95% CI, 1.1-5.0), serum albumin (ALB) of <36.4 mg/L (OR, 2.0; 95% CI, 1.6-3.4), and blood glucose (GLU) of >118 mg/dL (OR, 3.1; 95% CI, 1.1-5.3) were independent risk factors of postoperative SSI. With the application of sensitive and modifiable variables such as surgical duration and the levels of ALB and GLU, more geriatric patients with sub-high risk of postoperative SSI could be identified.
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